Tumour necrosis is a postoperative prognostic marker for pancreatic cancer patients with a high interobserver reproducibility in histological evaluation

• Published in: British journal of cancer 2010-09, Vol.103 (7), p.1057-1065
• Main Authors: Hiraoka, N, Ino, Y, Sekine, S, Tsuda, H, Shimada, K, Kosuge, T, Zavada, J, Yoshida, M, Yamada, K, Koyama, T, Kanai, Y
• Format: Article
• Language: English
• Subjects: 631/1647/1407/1555; 692/53/2422; 692/699/67/1504/1713; Antigens, Neoplasm - metabolism; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carbonic Anhydrase IX; Carbonic Anhydrases - metabolism; Carcinoma, Pancreatic Ductal - mortality; Carcinoma, Pancreatic Ductal - pathology; Cell Hypoxia; Drug Resistance; Epidemiology; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Middle Aged; Molecular Diagnostics; Molecular Medicine; Oncology; Pancreatic cancer; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - surgery; Postoperative Period; Prognosis; Reproducibility of Results; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6605854

Background: Tumour necrosis reflects the presence of hypoxia, which can be indicative of an aggressive tumour phenotype. The aim of this study was to investigate whether histological necrosis is a useful predictor of outcome in patients with pancreatic ductal carcinoma (PDC). Methods: We reviewed histopathological findings in 348 cases of PDC in comparison with clinicopathological information. We counted small necrotic foci (micronecrosis) as necrosis, in addition to massive necrosis that had been only defined as necrosis in previous studies. The reproducibility of identifying histological parameters was tested by asking five independent observers to blindly review 51 examples of PDC. Results: Both micronecrosis and massive necrosis corresponded to hypoxic foci expressing carbonic anhydrase IX detected by immunohistochemistry. Multivariate survival analysis showed that histological necrosis was an independent predictor of poor outcome in terms of both disease-free survival (DFS) and disease-specific survival (DSS) of PDC patients. In addition, metastatic status, and lymphatic, venous, and intrapancreatic neural invasion were independent prognostic factors for shorter DFS and metastatic status, margin status, lymphatic invasion, and intrapancreatic neural invasion were independent prognostic factors for DSS. The interobserver reproducibility of necrosis identification among the five independent observers was ‘almost perfect’ ( κ -value of 0.87). Conclusion: Histological necrosis is a simple, accurate, and reproducible predictor of postoperative outcome in PDC patients.